Development and application of synthetic methods for enantioselective synthesis of biologically active substances will be pursued. Specific areas of investigation include: ( 1 ) Chelation-controlled asymmetric intramolecular hydroformylation. Desymmetrization of prochiral dialkenyl carbinols and enones via temporary incorporation of recyclable or catalytic auxiliaries will exploit cumulative torsional, steric and electronic interactions in cyclic organometallic complexes to magnify the delta-delta G++ between enantiodifferentiating transition states. ( 2 ) Study of cation and radical initiated, vinylsilane terminated polyene cyclizations. These complementary conditions will be compared, each benefitting from stabilization of intermediate beta-silyl substitution on reactive intermediates. Conformational and orbital overlap requirements for the cationic and radical cyclizations will be probed. (3) Synthesis of polysubstituted hydropyrans via radical cyclization. Compact, relatively late transition states are projected for internal trapping of stabilized radicals by aldehyde or pyruvate carbonyls. Lewis acid effects on rate and stereoselectivity of cyclization will be examined. An iterative route to fused pyranopyrans is also proposed. (4) Total synthesis of nagilactone F, representative of a class of plant metabolites that exhibit antitumor and plant growth regulatory properties and insect larvae toxicity. Computational molecular modeling of intramolecular H-atom transfer reactions guides the synthetic strategy, which features a vinylsilane mediated polyene cyclization. (5) Total synthesis of neoliacinic acid, featuring an application of the radical cyclization route to polysubstituted hydropyrans and a metal-templated cyclization to form a bridging cyclooctenone. (6) Total synthesis of breynogenin, the aglycone of a potent in vivo, sulfur-containing hypocholesterolemic agent. Multiple epoxide openings are employed to establish the polyoxygenated cisfused perhydrothiaindane nucleus. A chelation-controlled glycolate enolate Claisen rearrangement is applied for acyclic stereocontrol.